Introduction
Following an agreed upon solvent etiquette is fundamental to our efficacy as a lab. Protocol should be optimized with regards to uninterrupted availability, space usage, waste reduction, and safety.
Etiquette
- When we are running low on a solvent, order more or ask someone else to. When you open a new bottle, check the stock of that solvent. This may include a trip to the solvent room.
- Before opening a new bottle, make sure there isn't one already open. For ethereal solvents, this is particularly important. Ethereal solvents, such as THF, diethyl ether, and 1,4-dioxane, form peroxides much more rapidly after opening. Uninhibited THF (used for cyclizations) should be consumed within a few months of opening.
- Do not leave the bottles open for longer than necessary. Solvent evaporates while water and dust enter.
- For anhydrous solvents that are sold in "resealable" bottles, it is generally frowned upon to unscrew the resealing lid. Use syringe/cannula transfer.
- When you are about to use a bottle of ethereal solvent, check the open date. You may need to test the solvent for peroxides or inform the LSR. Don't just put it back if you realize it's really old. If you don't feel comfortable testing it or it is so old that it is unsafe to open, ask someone else about what to do. If you see stuff floating in it or it's cloudy or there's crystallization, don't open the bottle. Tell the LSR.
- Keep your own secondary bottles. Label with the fill date if you think you might have it for awhile. That is, pour from the primary (4L) bottle into your own 0.5L bottle for your own use. Do not pipette out of a primary container.
When to order more
It takes a few days for solvents to arrive from Fisher's distribution center in Santa Clara. For the solvents in table 1, always make sure (whenever you open a new bottle, that we have enough unopened bottles left).
Table 1: heavy use (4 X 4L)| Solvent | When we order more (4L bottles remaining) | Grade | Usage |
| Acetonitrile (ACN) | 3 bottles remaining | HPLC | Heavy and very unpredictable |
| Dichloromethane (DCM) | 2 bottles remaining | ACS | Moderate and unpredictable |
| Acetone | 1-2 bottles remaining | ACS | Moderate and predictable |
| Dimethylformamide (DMF) | 1-2 bottles remaining | ACS | Moderate and predictable |
| Ethyl acetate (EtOAc) | 2 bottles remaining | ACS | Moderate and unpredictable |
| Hexanes | 1-2 bottles remaining | ACS | Low and unpredictable |
| Methanol (MeOH) | 2 bottles remaining | HPLC | Moderate and unpredictable |
| Isopropanol (iPrOH) | 1-2 bottles remaining | HPLC | Low-moderate and predictable |
In table 1, "unpredictable usage" is reserved for solvents that are used in chromatography. Chromatography consumes a lot of solvent quickly. Also, when a bottle is designated for chromatography use, it may be spiked with additives such as formic acid, acetic acid, or trifluoroacetic acid, rendering it unusable for any other application. This makes consumption rate even harder to predict.
Acetonitrile
Acetonitrile in particular is a multi-use solvent; used for reversed-phase chromatography, preparative HPLC, analytical HPLC, and peptide cyclization reactions. Running out of this solvent is relatively catastrophic - there is no good substitute for acetonitrile in HPLC. When you open a new bottle, check the cabinet and also the solvent room to make sure we have no fewer than three unopened bottles total. If we do have fewer than three unopened bottles, we need to order more. An entire 4L becomes limited-use upon addition of TFA or formic acid (automated chromatography unit and HPLC, respectively).
Dichloromethane
DCM is used as a wash solvent in SPPS, in silica gel chromatography, and reaction work-up.
Acetone
Acetone is mainly used to clean glassware. It is a powerful, broad-spectrum solvent. For most applications, it may be substituted for other available solvents.
Dimethylformamide
DMF is our primary peptide synthesis solvent. It is used frequently in small volumes, making overall use relatively constant. Because DMF is a staple, running out is bad.
Ethyl acetate
EtOAc is used in reaction work-up and chromatography. Chromatography may demand large volumes suddenly.
Hexanes
Hexanes is used mainly in silica gel chromatography. Since we prefer reversed-phase chromatography, we don't use very much hexanes.
Methanol
Methanol is used mainy as a solvent for HPLC samples, an HPLC wash solvent, and for reversed-phase chromatography. For large-scale purifications, it is preferred over acetonitrile because it is cheaper.
Isopropanol
Isopropanol is used mainly as an HPLC wash solvent. It tends to be consumed slowly.
Table 2: other frequently used solvents (should be kept in stock)| Solvent | Grade | When we order more | Usage rate | Storage considerations? |
| Tetrahydrofuran (THF) | ACS, anhydrous (inhibited with BHT) | 1 unopened bottle (1L) | Moderate and predictable | ETHEREAL |
| Tetrahydrofuran (THF) | HPLC (uninhibited) | 1 unopened bottle (1L) | Unpredictable | ETHEREAL AND UNINHIBITED |
| 1,4-Dioxane | ACS, anhydrous or unspecified (inhibited with BHT) | 1 unopened bottle (0.5 or 1L) | Low and unpredictable | ETHEREAL |
| Diethyl ether | ACS, anhydrous or unspecified (inhibited with BHT) | 1 unopened can (1L) | Low and unpredictable | ETHEREAL |
| Toluene | ACS | 1 unopened 4L bottle | Low | none |
| Trifluoroacetic acid (TFA) | 99% | 100mL or so | Low and predictable | none |
| Formic acid (FA) | 99% | 100mL or so | Low and predictable | none |
| Hexafluoroisopropanol (HFIP) | whatever | 100 mL or so | Low and predictable | none |
| Ethanol | ? | ? | ? | none |
| Dimethyl sulfoxide (DMSO) | 99.9% | as needed | Low | none |
In table 2, many of the solvents are ethereal. Ethereal solvents accumulate peroxides upon exposure to air and light. This means that after opening, a bottle can only be kept for a short time (a few to several months). Do not open bottles if there is already one open. Unopened bottles may be kept for 18 months. Both inhibited/anhydrous and uninhibited THF are listed because both should be kept in stock. Inhibited/anhydrous THF is used in synthesis, while uninhibited THF is used for cyclizations.